DESCRIPTION, OVERALL (provided by applicant): Despite years of research and a considerable monetary expenditure the pathophysiology of the Urologic Chronic Pelvic Pain Syndrome (UCPPS) known as Interstitial Cystitis/Painful Bladder Syndrome (IC/PBS) remains elusive. This University of Iowa MAPP grant proposal is intended to study this condition from a new perspective. The proposal is designed around the general hypothesis that patients with IC/PBS bladder symptoms and a co-morbid condition like fibromyalgia (FM) or irritable bowel syndrome (IBS) have systemic basis for their symptoms and are fundamentally different from patients with IC/PBS bladder symptoms alone. We based our general hypothesis on the previous work of the investigators in this MAPP application which is detailed in subsequent sections. During the program project planning and design phase for the 5 projects proposed in this grant, all investigators worked from this general hypothesis. The proposed work is important because of its novel nature and the synergy and horizontal integration among the 5 proposed projects. The projects were planned to examine the heterogenous condition of IC/PBS. The cohorts of patients to be studied are similar across all clinical projects and include patients with IC/PBS symptoms in the bladder only, patients with IC/PBS bladder symptoms and a systemic co-morbid condition (FM, IBS), patients with only a co-morbid condition (FM.IBS) and healthy controls. The basic science projects reinforce and expand the scope of the clinical projects by utilizing biologic specimens collected in the clinical projects to add basic cellular, molecular and biochemical understanding of the UCPPS syndrome (IC/PBS). The Project proposals examine the UCPPS of IC/PBS from a multifaceted perspective. Subsequent data analysis of this Discovery Site project will describe the phenotype and risk factors of each group related to the HPA axis, stress response, neurophysiology, pain pattern, biologic and behavioral predisposing factors, basic immunology and biochemistry.